The long-term goals are to understand human pathogenesis of Bacillus anthracis, which has potential for use in bioterrorism. Our studies are also directed towards identifying methods to prevent production of virulence factors by this organism to cause disease. We have shown bacterial surface-active agents, glycerol monolaurate and chitosan malate, preventing production of the superantigens when produced in B. subtilis. In addition, we have suggested (with success) that patients with inhalation anthrax be treated with clindamycin in addition to other therapy because of the antibiotic's known ability to inhibit gram positive exotoxin production at sub-bacterial inhibitory levels. We have shown that Staphylococcus aureus requires oxygen and carbon dioxide in its external environment for maximal production of TSST-1. This observation led to our identification of a two-component regulatory system that is involved in oxygen control of superantigen production by the organism. We have shown that over-expression of this system, designated srrA/B (for staphylococcal respiratory response), in S. aureus significantly represses superantigen production. By computer analysis we identified a Bacillus anthracis homolog of SrrA-SrrB, tentatively designated BrrA-BrrB, and hypothesize that this two-component regulatory system is important in controlling anthrax toxin and capsule production. Furthermore, we hypothesize that BrrA-BrrB is an important target for the action of glycerol monolaurate and chitosan malate. In this application we propose one specific aim: 1) to characterize BrrA-BrrB and its effect on production of B. anthracis toxin and capsule. We hypothesize that this system functions as a repressor of genes for both virulence factors. Over-expression of the system will interfere with production of exotoxin and capsule by the organism, even under highly aerobic conditions. Finally, we hypothesize that exotoxin and capsule production will be suppressed by both glycerol monolaurate and chitosan malate through activation of BrrA-BrrB.